Washburn Lab

Michael Washburn, Ph.D.

Director of Proteomics Center

Professor, Department of Pathology & Laboratory Medicine
  The University of Kansas Medical Center

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According to Michael Washburn, Ph.D., his job description is simple: “To read, write and talk.” As director of the Stowers Proteomics Center, he sees his primary responsibility as staying on top of protein technology and deciding which new technologies to bring to Stowers.

The MudPIT cycle starts from a protein mixture and ends with the determination of protein identities and relative levels within the initial mixture. MudPIT is characterized by six main steps: 1) sample preparation by the user;

2) digestion of proteins into peptides; 3) resolution of peptides by multidimensional chromatography; 4) fragmentation of eluting peptide ions by tandem mass spectrometry; 5) database matching of acquired tandem mass spectra to peptide sequences; 6) in-depth data analysis.

Image: Courtesy of Dr. Michael Washburn

In today’s biology, however, keeping current on protein technology is anything but simple. Since the mid-90s there has been a shift in molecular biology from focusing on what a single protein does to understanding how large networks or complexes containing multiple proteins assemble and interact within a cell. That shift has given rise to a new field—proteomics—defined as the study of the structure, function and interactions of all proteins contained in a cell.

Washburn is a leader in applying mass spectrometry techniques to identify and quantify protein interactions, so much so that in July of 2011 he was named a “Rising Star in Molecular Biology and Genetics” by Thomson Reuters Science Watch.

Raised in St. Paul, Washburn became interested in chemistry in high school and earned a BA in Chemistry in 1992 from Grinnell College in Iowa. For graduate school he chose Michigan State where he obtained a Ph.D. in biochemistry and environmental toxicology with William Wells in 1998.

For his thesis Washburn undertook biochemical analyses of glutaredoxin, but was casting around for something new to tackle as a postdoc. Around then he heard a lecture about mass spectroscopy by Fred McLafferty, then a chemist at Cornell, who was a pioneer in the development of protein mass spectrometry.

Inspired by the talk to learn a new technology applicable to proteomics, Washburn signed up to postdoc with  pioneering proteomics scientist John Yates, then at the University of Washington. A decision, Washburn remembers, some colleagues advised against. “Several people told me that I shouldn’t do a postdoc in protein  mass spectroscopy—that there was no future in it,” he says. That advice turned out to be tantamount to saying there is no future in silicon chips.

Soon after, Washburn accompanied Yates when he relocated to Scripps Research Institute in La Jolla where Washburn worked with him at the nearby Torrey Mesa Research Institute. During that time, Washburn, Yates and collaborator Dirk Wolters published a pair of highly cited papers in Nature Biotechnology and Analytical Chemistry in which they analyzed the entire collection of proteins—or “proteome”—of the yeast Saccharomyces cerevisiae using a novel mass spec technology called MudPIT, for Multi-dimensional Protein identification Technology.

MudPIT’s innovation was hooking up a liquid chromatograph to a mass spectrometer rather than using conventional two-dimensional gel approaches as a source of starting material. “The merge of several years of chromatography research with years of spectrometry made this technique extremely powerful,” says Washburn. “Plus, the timing was right!” That the paper has been cited more than 2200 times since its publication underscores that point.

Recruited to Stowers in 2003, Washburn continues to modify MudPIT and has developed a method called normalized spectral abundance factor (NSAF) or “spectral counting” to determine not only the identity but the abundance of proteins in a complex. Washburn applied NSAF to quantify expression changes in yeast proteins in a 2006 Journal of Proteome Research study and teamed up with Stowers investigators Ron and Joan Conaway to analyze subtypes of the transcriptional regulatory complex Mediator in a 2006 PNAS paper.

The Mediator study reflects Washburn’s newfound interest in transcription, an area he had no training in before coming to Stowers. “I was always interested in mechanistic biology but here I was exposed to an outstanding group of scientists working in the transcription field,” he says. That prompted Washburn to do what his mother always told him: “Grow where you’re planted.”

Combinatorial depletion analysis to assemble the network architecture of chromatin remodeling complexes. Hierarchical clustering was performed on abundance values measured for proteins isolated from strains deleted for various subunits of the SAGA and ADA complexes. The clustering results led to the formation of distinct modules within the SAGA and ADA complexes.

Image: Courtesy of Dr. Michael Washburn

In recent years, Washburn, working together with his wife biochemist Laurence Florens, who heads the proteomics core within the center, has often collaborated with the Conaways, Ali Shilatifard, and Jerry Workman to study transcription and chromatin remodeling.

One collaboration with the Workman lab resulted in a 2011 Molecular Systems Biology study that defined modules comprising the multi-protein SAGA chromatin remodeling complex, an analysis that provides clues to how the complex is assembled.  “I think that study has a future in guiding structural biology,” says Washburn. “Here we can take a large protein complex and make it amenable to crystal structure analysis.”

Washburn calls working at Stowers a rare opportunity, in terms of resources and launching something new.  “The process of building a new institute is so much more fun than maintaining the reputation of a place already established,” he says.

But he disagrees with a colleague’s characterization of Stowers as a “Disneyland for scientists” saying, “I don’t think Disneyland deserves that much credit.”